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Dissertation
Localizing the diabetes susceptibility gene, Iddm4, in the biobreeding diabetes-resistant (BBDR) rat
Doctor of Philosophy (Ph.D.), Drexel University
Apr 2003
DOI:
https://doi.org/10.17918/00000652
Abstract
The Iddm4 locus, on rat chromosome 4, is possibly the strongest non-major histocompatibility complex determinate of susceptibility to type one diabetes in the BioBreeding (BB) rat. Viral antibody-free BBDR and WF rats do not spontaneously develop diabetes. Perturbation of the immune system does however, induce diabetes in BBDR rats. Iddm4 is genetically linked with diabetes in BBDR rats treated with a viral mimic, polyinosinic:polycytidylic acid, and an antibody that depletes Art2 + regulatory cells. Current efforts focus on positioning Iddm4 and evaluating Iddm4 candidate genes. We have developed lines of WF. Iddm4 congenic rats. Testing the progeny of WF. Iddm4 congenic rats with recombinant segments of chromosome 4 for susceptibility to induced diabetes has localized the Iddm4 gene to a <2.8 cM interval, flanked by D4Rat135 and D4Got51 markers. We have constructed genetic and physical (radiation hybrid) maps of this interval. Using these maps and the available genome data bases (UCSC Genome Browser and NCBI), we have identified a comprehensive list of known genes and expressed sequence tags (ESTs) in the Iddm4 interval. We have designed an Iddm4 interval/immunochip DNA microarray representing 130 genes and ESTs. This microarray contains 67 genes that map to the Iddm4 interval, 43 immune-related genes, 17 TCR V-beta (Tcrv-beta) genes, and three house-keeping genes. Rat 5K DNA arrays, representing nearly 5,000 genes were used for comparison. Using these Iddm4 interval/immunochip DNA microarrays, we have profiled gene expression in the spleens and thymus of untreated, nondiabetic WF. Iddm4d vs. WFIddm4w congenic rats. Results from the Iddm4 interval/immunochip DNA microarrays suggest that, of all genes on the array, only Vbeta4 may be differentially expressed in the thymus of these rats; no differentially expressed genes were detected in the spleens.
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Details
- Title
- Localizing the diabetes susceptibility gene, Iddm4, in the biobreeding diabetes-resistant (BBDR) rat
- Creators
- Cheryl DeScipio
- Contributors
- Elizabeth P. Blankenhorn (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 122 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991014970316304721